In human leukemia and lymphoma, chromosome translocations disrupt adjacent proto-oncogenes, contributing to oncogenesis. The bcl-1 region on chromosome 11 has been defined as the location of breakpoints of the t(11;14)(q13:q32) translocation. This translocation has been associated with several types of B-cell lymphocytic lymphoma, including more than 50% of a common subtype called centrocytic (or intermediate) lymphoma. We have located the bcl-1 gene in this region of genomic DNA and determined it to be a member of the cyclin gene family. As such, it is likely to play an important role in cell-cycle progression. In this proposal we will finish our analysis of cDNA clones from this gene, determine its genomic structure and initiate studies to determine its function. While this proposal has great importance for the study of human leukemia and lymphoma, the bcl-1 gene may also have importance for a variety of solid cancers, including breast cancer. Evidence already exists that the bcl-1 locus from chromosome 11 is amplified in breast cancer, esophageal cancer, head and neck cancer, and others. We believe that the bcl-1 gene may be driving this amplification. therefore, it is our hypothesis that the bcl-1 gene is an important gene for several types of malignancy. More complete information about the bcl-1 gene will aid our understanding of how lymphomas and solid cancers arise. As bcl-1 is a member of the cyclin gene family, the close relationship that exists between the fields of cell-cycle control and cancer is dramatically emphasized. This raises the hope that new ways to manipulate the cell cycle will lead to additional advances in our ability to treat cancer.